Breast cancer is a leading cause of cancer-related deaths in women in the United States and worldwide. Inherited genetic variations, or gene polymorphisms, are viewed as major factors in breast cancer prevalence.
A number of breast cancer susceptibility genes have been identified. The two most important breast cancer susceptibility genes, BRCA1 and BRCA2, accounted for approximately 15% of breast cancer cases due to inherited mutations or alterations. However, BRCA1 and BRCA2 mutations are present in far less than 1% of the general population. In addition to BRCA1 and BRCA2, five other genes, TP53, PTEN, LKB1, ATM and CHEK2, are also well established breast cancer susceptibility genes. The proportion of breast cancer in the general population explained by these gene mutations is very small. It is estimated that all the currently known breast cancer susceptibility genes accounts for less than 25% of the familial aggregation of breast cancer. The evidence to date strongly suggests that the majority of the familial clustering of breast cancer is unexplained and other breast cancer susceptibility genes still remain to be identified. The identification of new genes could make a major impact in risk prediction.
CD44 is a cell surface transmembrane glycoprotein, encoded by a single gene. Transcripts for CD44 gene undergo complex alternative splicing that results in many functionally distinct isoforms. Recent experimental and clinical evidence shows that CD44 and its interaction with hyaluronan may regulate breast cancer cell proliferation, migration, and invasion, as well as tumor-associated angiogenesis and are correlated with patient survival. Thus, CD44 polymorphisms play an important role in breast cancer development.